OP0217 EFFECTIVENESS AND SAFETY OF IL-6 INHIBITION (TOCILIZUMAB) VERSUS TUMOUR NECROSIS FACTOR INHIBITION IN POLYARTICULAR JUVENILE IDIOPATHIC ARTHRITIS: RESULTS FROM THE OBSERVATIONAL BIKER STUDY
Authors: A. Klein, A. Zimmer, T. Hospach, F. Weller-Heinemann, S. Hansmann, J. Kuemmerle-Deschner, M. Fasshauer, K. Minden, I. Foeldvari, C. Rietschel, D. Windschall, R. Trauzeddel, M. Hufnagel, D. Foell, R. Berendes, G. Boeschow, P. Oommen, F. Dressler, G. Horneff
Journal: Annals of the Rheumatic Diseases (2022)

Background Tocilizumab (TCZ) has been approved for treatment of juvenile idiopathic arthritis (JIA) for 10 years. Objectives Evaluation of 12-month efficacy and safety of TCZ compared to TNF inhibitors (TNFi). Methods BIKER WA 29358 is a 5-year multi-centre prospective, observational cohort study including polyarticular JIA patients in Germany starting treatment between 2015 and 2020 with TCZ and matched 1:1 by date of treatment start and region to patients starting an approved TNFi. Clinical disease activity (JADAS10), JADAS MDA (≦3.8)/remission (≦1.0), safety and drug adherence at 12 months were assessed and compared between cohorts. Results The analysis included 342 participants with 12-month treatment data (TCZ n=171; TNFi n=171). TCZ was used as 2nd line biologic in the majority of patients (84%) while TNFi were mostly 1st line biologics (86%). Patients starting TCZ had a longer disease duration. Efficacy was demonstrated by a marked decrease in JADAS10 in both cohorts (TCZ vs. TNFi at baseline: 15.0+/-6.7 vs. 14.6+/-6.3; at month 12: 3.8+/-5.1 vs. 3.4+/-4.5). Proportions of patients in TCZ/TNFi cohorts achieving JADAS remission at 12 months were 48%/41% in 1st line biologic users and 32%/33% in 2nd line biologic users. JADAS MDA was achieved in 64%/69% in 1st line and 52%/58% in 2nd line users of TCZ/TNFi. After 12 months of treatment JADAS10 (mean +/SD) was higher in the 2nd line TNFi cohort compared to the 1st line (4.5+/-5.6 vs. 3.2+/-4.3), similar to patients receiving 2nd or 1st line TCZ (4.0+/-5.2 vs. 2.9+/-4.4). Patients receiving TCZ or TNFi as first biologic reached JADAS10 remission and MDA numerically more frequently but not statistically significant compared to 2nd line users. Safety was assessed based on adverse event (AE) reporting. 57 (33%) patients in the TCZ cohort and 43 (25%) patients in the TNFi cohort reported AE. The AE rate was significantly higher in the TCZ cohort (69 vs. 44.8/100 patient years, RR 1.5 [95%CI 1.1-2.0], p=0.006, Wald-test). There were 6 serious AE in the TCZ and 3 in the TNFi cohort. Injection site reactions were more common in the TNFi cohort (9 vs. 1, p=0.043). No further differences were identified to date. There was no death and no opportunistic infection. In the TCZ cohort, 32 patients discontinued treatment, 27 due to lack of efficacy, while in the TNFi cohort only 6 patients discontinued treatment. Treatment discontinuation was more frequent among the 2nd biologic users (n=29; 17.4%) than in first line users (n= 9; 5.1%). Conclusion In this first interim analysis, treatment targets were reached with similar frequency after 12 months of treatment with TCZ or TNFi. TCZ was used predominantly as 2nd line biologic. Higher rates of remission /MDA were observed in 1st line compared to 2nd line biologic users. Although more AE were reported in the TCZ cohort, the occurrence of serious AE and infections was comparable in both cohorts. No new safety signals were identified. Observation is ongoing. Table 1. Baseline characteristics and discontinuations with reasons. Number, n TNFi 1 st 147 TNFi 2 nd 24 TNFi total 171 TCZ 1 st 27 TCZ 2 nd 144 TCZ total 171 Female, % 119(81%) 20 (83%) 139(81%) 20(74%) 123(85%) 143(84%) Disease duration, years 2.7+/-2.7 6.5+/-3.3 3.2+/-3.1 2.5+/-2.7 5.9+/-4.1 5.4+/-4.1 Pre-treatment n.a. None=147 (86%) n.a. None=27 (16%) 1 biologic 14 (58%) 14 (8%) 80 (56%) 80 (47%) 2 biologics 7 (29%) 7 (4%) 54 (38%) 54 (32%) ≥ 3 biologics 3 (13%) 3 (2%) 10 (7%) 10 (6%) CHAQ-DI, mean +/- SD 0.67+/-0.64 0.31+/-0.45 0.63+/-0,63 0.43+/-0.44 0.65+/-0.65 0.61+/-0.62 JADAS 10, mean +/- SD 14.8+/-6.3 13.4+/-6.8 14.6+/-6.3 13.3+/-6.0 15.3+/-7.0 15.0+/-6.7 Concomitant MTX, n (%) 120 (82%) 13 (54%) 133 (78%) 17 (63%) 75 (52%) 92 (54%) Steroid, n (%) 37 (25%) 4 (17%) 41 (24%) 8 (30%) 35 (24%) 43 (25%) Discontinuations, n (%) 5 (3.4%) 1 (4.2%) 6 (3.5%) 4 (16%) 28 (19%) 32 (19%) -Inefficacy 1 (0.7%) 2 (1.2%) 3 (12%) 24 (17%) 27 (16%) -Intolerance 2 (1.4%) 1 (4.2%) 2 (1.2%) 2 (1.4%) 2 (1.2%) -Other 2 (1.4%) 2 (1.2%) 1 (4%) 4 (2.8%) 5 (3.0%) Disclosure of Interests Ariane Klein Speakers bureau: Novartis fee chairing a lunch symposium, Angela Zimmer: None declared, Toni Hospach: None declared, Frank Weller-Heinemann: None declared, Sandra Hansmann: None declared, Jasmin Kuemmerle-Deschner: None declared, Maria Fasshauer: None declared, Kirsten Minden Speakers bureau: Honoraries from Novartis, Pfizer, Medac, Ivan Foeldvari: None declared, Christoph Rietschel: None declared, Daniel Windschall Speakers bureau: Pfizer, Novartis, Abbvie, MEDAC, Canon, Grant/research support from: Novartis, Pfizer, Ralf Trauzeddel: None declared, Markus Hufnagel: None declared, Dirk Foell: None declared, Rainer Berendes: None declared, Gundula Boeschow: None declared, Prasad Oommen: None declared, Frank Dressler Speakers bureau: Honoraries from Novartis, Pfizer, Abbvie, Consultant of: Advisory board Novartis, Mylan, Gerd Horneff Speakers bureau: Novartis, Pfizer, Janssen, Grant/research support from: Pfizer, Novartis, Roche, MSD